1. Field of the Invention
The invention relates generally to a vascular implant and, more specifically, to a multiple drug-eluting intravascular implant and methods of using the implant to perform percutaneous transluminal coronary angioplasty and intracerebral vessel repair at target lesions for the treatment of heart disease and cerebrovascular pathology associated with vascular occlusions.
2. Background Information
Percutaneous transluminal coronary angioplasty (PCTA) is a procedures which is well established for the treatment of blockages, lesions, stenosis, thrombus, and the like, which may be present in body lumens such as the coronary arteries and other vessels.
A widely used form of percutaneous coronary angioplasty makes use of a dilation balloon catheter which is introduced into and advanced through a lumen or body vessel until the distal end thereof is at a desired location in the vasculature. Once in position across an afflicted site, the expandable portion of the catheter, or balloon, is inflated to a predetermined size with a fluid at relatively high pressures. By doing so, the vessel is dilated, thereby radially compressing the atherosclerotic plaque of any lesion present against the inside of the artery wall, and/or otherwise treating the afflicted area of the vessel. The balloon is then deflated to a small profile so that the dilation catheter may be withdrawn from the patient's vasculature and blood flow resumed through the dilated artery.
In angioplasty procedures of the kind described above, there may be restenosis of the artery, which either necessitates another angioplasty procedure, a surgical by-pass operation, or some method of repairing or strengthening the area. To reduce restenosis and strengthen the area, a physician can implant an intravascular prosthesis for maintaining vascular patency, such as a stent, inside the artery at the lesion.
Stents, grafts, stent-grafts, vena cava filters and similar implantable medical devices, collectively referred to as stents, are radially expandable endoprostheses which are typically intravascular implants capable of being implanted and enlarged radially after being introduced. Stents may be implanted in a variety of body lumens or vessels such as within the vascular system, urinary tracts, bile ducts, and the like. Stents may be used to reinforce body vessels and to prevent restenosis following angioplasty in the vascular system. They may be self-expanding, such as a nitinol shape memory stent, mechanically expandable, such as a balloon expandable stent, or hybrid expandable.
Pharmaceutical compounds may be coated directly on the stent to provide an efficacious point-of-use drug delivery system. Such systems can be used to prevent insertion induced complications that may include inflammation, infections, thrombosis or blood clots, restenosis, and proliferation of cell growth, where such growth may occlude passageways.
One approach has been to coat the stents with various anti-thrombotic or anti-restenotic agents in order to reduce thrombosis and restenosis. For example, impregnating stents with radioactive material appears to inhibit restenosis by inhibiting migration and proliferation of myofibroblasts. Irradiation of the treated vessel can pose safety problems for the physician and the patient. In addition, irradiation does not permit uniform treatment of the affected vessel.
Alternatively, stents have also been coated with chemical agents such as heparin or phosphorylcholine, both of which appear to decrease thrombosis and restenosis. Although heparin and phosphorylcholine appear to markedly reduce restenosis in animal models in the short term, treatment with these agents appears to have no long-term effect on preventing restenosis. It is not feasible to load stents with sufficient therapeutically effective quantities of either heparin or phosphorylcholine to make treatment of restenosis in this manner practical.
Synthetic grafts have been treated in a variety of ways to reduce postoperative restenosis and thrombosis. For example, composites of polyurethane such as meshed polycarbonate urethane have been reported to reduce restenosis as compared with expanded polytetrafluoroethylene (ePTFE) grafts. The surface of the graft has also been modified using radiofrequency glow discharge to add polyterephalate to the ePTFE graft. Synthetic grafts have also been impregnated with biomolecules such as collagen. However, none of these approaches has significantly reduced the incidence of thrombosis or restenosis over an extended period of time.
Synthetic grafts have also been seeded with endothelial cells, but the clinical results with endothelial seeding have been generally poor, i.e., low post-operative patency rates. Further, although drug-eluting (DE) coronary artery stents have shown superior short- and mid-term results in lower rates of neovascularization compared to bare metal (BM) stents, long term (≧2 years) restenosis rates over 5-15% at 3 year post-procedure are still considerable due to “late thrombosis,” and are not significantly better than BM stents in certain patient groups. For example, in diabetic patients, restenosis rates of DE stents are as high as 20-30%, and these rates are even higher for BM stents for this group.
The addition of a coating of anti-inflammatory or anti-proliferative drugs to BM stents has resulted in improved performance of these stents in their role to “prop-open” previously clogged arteries, compared to uncoated BM stents, in reducing the risk of early or mid-term re-blockage. However, patients with the most severe forms of atherosclerosis still have high rates of re-blockage after stent implantation, in spite of the use of DE stents.